Nuclear and chromosomal non-histone proteins of rat liver have been examined in detail by two-dimensional gel electrophoresis and many hundred polypeptides identified. The changes in the pattern of these proteins in nuclear washes compared to chromatin and nuclear matrix proteins have been determined. The identification of the function of many of these proteins is in progress. The grant focuses upon those proteins which may be involved in gene regulation by determining those which preferentially bind to homologous versus heterologous DNA. The problem of "non-operator binding" of proteins to heterologous DNA is approached by various procedures involving exchange of non-histone proteins from preliminary binding to heterologous DNA to secondary binding to homologous DNA.